Medical instrument

ABSTRACT

The blood flow channel sections of an oxygenator and a blood reservoir are hydrophilized by treatment with an acid, an albumin solution, polyhydroxy methacrylate, corona discharge, plasma or ozone, so that it has highly improved wettability by the priming liquid and the blood to prevent blood foaming. The blood flow channel sections of a medical instrument may be additionally hydrophilized by treatment with a polymer containing hydroxyethyl methacrylate and methyl methacrylate or in addition thereto a poly(oxyethylene)-poly(oxypropylene) block polymer.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to a blood reservoir or a hollow fibre typeoxygenator in which the blood flow channel section of the bloodreservoir or at least a fraction of the outer wall surfaces of thehollow fibre of the oxygenator is subjected to a chemical treatment suchas with acid or albumin solutions or polyhydroxyethyl methacrylate,hereafter referred to as PHEMA, discharge treatment such as by corona orplasma treatment or with ozone and thereby hydrophilized to improvewettability thereof with the blood.

This invention also relates to medical implements or instruments inwhich the blood flow channel sections are hydrophilizingly treated usinga polymer such as hydroxyethyl methacrylate (HEMA), methyl methacrylate(MMA) of using poly(oxyethylene)-poly(oxypropylene) block polymer aftertreated using above polymer.

2. Prior Art

Various polymers employed in the materials of medical implements aregenerally of hydrophobic properties. However, depending on usage andapplications, not few of these materials require a hydrophilizingsurface treatment.

In an oxygenator, for example, the housing is divided by a gas exchangemembrane into two sections and a gas exchange is effected between theblood flowing in one of these sections and the gas, mostly oxygen,flowing in the other section. As a gas exchange membrane, polypropylene,polystyrene or silicone membranes, exhibiting hydrophobic properties,are frequently employed.

It is noted that, before using the oxygenator, a priming operation isusually carried out to remove the air contained in the oxygenator. Themembrane is hydrophobic and exhibits only poor affinity with water sothat the air cannot be eliminated completely in the course of thepriming operation. Above all, in the case of a hollow fibre typeoxygenator employing porous hollow fibre as the gas exchange membrane,with the blood being caused to flow outside of the hollow fibre, thereis demonstrated a strong tendency for the air to become trapped betweenthe adjacent fibers of the hollow fibre. The result is that theseadjacent fibers become flocculated by the air to form so-called cavitiesto lower the gas exchange performance.

The majority of the hollow fibre type oxygenators hitherto evolved wereof the type in which the blood is caused to flow within the inside ofthe hollow fibre. However, because of large pressure losses encountered,it is felt that this type of the oxygenator can be applied to pulsedflow excorporeal circulation, separate excorporeal circulation or bloodcardioplegia, only with considerable difficulties.

When the blood and the gas are caused to flow outside and inside of thehollow fibre, respectively, pressure losses may be lowered, so that theblood can be supplied to the oxygenator and thence to the bloodreservoir by blood movement caused only by the pressure head from thepatient's body without the necessity of providing a blood delivery pumpahead of the oxygenator in the circulating circuit. In this manner, theoxygenator can be adapted to blood cardioplegia or to separateexcorporeal circulation.

With the hollow fibre formed by a hydrophobic resin, the fibre surfaceexhibits only low wettability by the blood, so that the blood cannot bedistributed satisfactorily between the adjacent hollow fibre. Hence aneffective gas exchange via the hollow fibre is obstructed and asufficient gas exchange performance is not achieved. For wetting theouter wall surfaces of the hollow fibre, the air bubbles remainingbetween the hollow fibre need be removed by imparting as physical shock,such as by a laborious operation of striking the oxygenator.

In open heart surgery, a blood circuit with a built-in oxygenator isused in place of the living lung to eliminate carbon dioxide in theblood and to replenish oxygen in excorporeal circulation.

In the excorporeal blood circulation circuit with the built-inoxygenator, a blood reservoir is provided to eliminate air bubblesoccasionally flowing int the circuit or to store and replenish the bloodin the event of possible decrease in the blood circulation caused by,for example, tube rupture in the circuit.

In view of relative ease with which the stored blood quantity can beascertained and the blood of a large volume can be stored, a hard shelltype blood reservoir, formed of a hard material, is generally employed.Since the blood reservoir can then be incorporated easily into theoxygenator, there is proposed an oxygenator with a build-in bloodreservoir.

However, when the blood reservoir exhibits hydrophobic properties, theblood or the priming liquid is not allowed to flow uniformly on theoverall surface of the blood flow channel, but flows as a partializedflow into the blood reservoir to produce air bubbles.

The hard shell type blood reservoir 1 integrated to the oxygenator isshown diagrammatically in FIG. 1 and formed by a housing 7 formed of ahard material and including a blood inlet port 2, a blood influentsection 5 communicating with the inlet port and presenting a bottomsurface having substantially no drop from the inlet port 2, a bloodreservoir section 6 communicating with the blood influent section andpresenting a bottom surface gradually descending from the section 5 anda blood outlet 3 formed at the bottom of the reservoir section 6. It isnoted that the bottom surfaces of the blood influent section 5 and theblood reservoir section 6 and the lateral sides of the housing 7represent a blood flow channel surface.

The blood introduced via the blood inlet port 2 is caused to flow on theblood flow channel surface 4 so as to descend to and be stored in theblood storage section 6.

Heretofore, the housing 7 of the blood reservoir 1 was formed by amember of a material exhibiting hydrophobic properties, such as, forexample, hard vinyl chloride resin, styrene resin or carbonate resin. Asa result, the blood flow channel surface 4 also exhibited hydrophobicproperties, so that, on performing bloodless priming, the priming liquidwill flow as a partialized flow without flowing uniformly on the overallblood flow channel surface 4. In this manner, the liquid flow will bedisturbed and the priming liquid flows into the blood storage section 6just like a fall flows down into a pond to produce the air bubbles orfoam in the blood storage section 6. In addition, the above materialsare not said to be satisfactory in compatibility to the blood.

It will be noted that the filter medium for removal of foreign matter ofa blood filter or arterial filter provided downstream of the excorporealcirculating circuit is in the form of pleats, for elevating theproperties of removal of foreign matter, s that air bubbles cannot beremoved easily. Also, since the materials are hydrophobic, they are lowin wettability, so that a certain pressure head is necessitated in thepriming operation, which renders the priming operation difficult.

For combatting the above deficiency and improving wettability of theblood flow channel surface by the blood or the priming liquid, attemptshave been made to hydrolyze the blood flow channel surface by a suitablesurface treatment. However, these attempts have not met with successbecause of difficulties in simultaneously achieving uniform hydrophilicproperties and improved compatibility to the blood without changing theproperties of the material.

It is therefore an object of the present invention to provide anoxygenator in which the outer wall surface of the hollow fibre ishydrophilized to improve wettability thereof by the blood and thepriming liquid to suppress formation of air bubbles without lowering thegas exchange properties.

It is another object of the present invention to provide a bloodreservoir in which the blood flow channel surface is hydrophilized inpart or in its entirety to improve wettability thereof by the blood andthe priming liquid to suppress generation of air bubbles or foam by theblood flowing into the blood storage section.

The present invention has been fulfilled as a result of out perseverantresearches for combatting the above deficiencies mainly caused by thehydrophobic properties of the blood flow channel sections of the medicalinstruments. It is an object of the present invention to provide amedical instrument in which at least the blood flow channel sectionthereof is subjected to a hydrophilizing treatment to improvewettability thereof by the blood or by the priming liquid to preventaffixture of air bubbles while simultaneously improving compatibility tothe blood of the medical instrument.

The present invention has been fulfilled as a result of our perseverantresearche for eliminating the above deficiencies mainly caused by thehydrophobic properties of the blood flow channel sections of the medicalinstrument. It is another object of the present invention to provide amedical instrument in which at least the blood flow channel sectionthereof is subjected to a hydrophilizing treatment to improvewettability thereof by the blood or by the priming liquid whilesimultaneously improving compatibility to the blood of the medicalinstrument.

DISCLOSURE OF THE INVENTION

According to a first aspect of the present invention, there is provideda hollow fibre type oxygenator in which the outer sides of the fibre areused as the blood flow channel, wherein at least some of said hollowfibres have the outer wall sides thereof hydrophilizingly treated sothat air bubbles can be affixed to the outer wall sides of the hollowfibres only difficultly.

Preferably, the hollow fibre is a polyolefinic resin and thehydrophilizingly treated hollow fibre has such properties that theliquid surface is raised along the outer walls of the hollow fibre whenone of the hollow fibres is introduced into water from a directionnormal to the water surface.

According to a second aspect of the present invention, there is provideda blood reservoir comprising a blood flow channel surface inclined atleast partially, a blood influent section located upstream of said bloodflow channel surface, a blood storage section located below said bloodflow channel surface, and a blood effluent section located downstream ofsaid blood storage section, wherein said blood flow channel surfaceexhibits hydrophilic properties so that the blood introduced into thereservoir via the blood influent section and flowing down on the bloodflow channel surface will flow substantially uniformly on the surface inits entirety without exhibiting the tendency to form a partialized flowon said surface.

The contact angle of the blood blow channel surface exhibiting thehydrophilic properties with respect to water is preferably less than 90°and more preferably not more than 80°.

According to a third aspect of the present invention, there is provideda medical instrument wherein at least the blood flow channel sectionthereof is coated in part or in its entirety by a polymer containinghydroxyethyl methacrylate (HEMA) and methyl methacrylate (MMA).

Preferably, hydroxyethyl methacrylate (HEMA) and methyl methacrylate(MMA) exist separately as respective separate segments. Preferably, theweight ratio of the segments containing hydroxyethyl methacrylate (HEMA)to the segments containing methyl methacrylate (MMA) is 50:50 to 95:5.More preferably, the content of hydroxyethyl methacrylate (HEMA) in saidsegment containing hydroxyethyl methacrylate (HEMA) is not less than 50wt. % and the content of methyl methacrylate (MMA) in said segmentcontaining methyl methacrylate (MMA) is not less than 70 wt. %.

Preferably, the medical instrument is an oxygenator and the blood flowchannel section is the outer wall of porous hollow fibre housed withinthe oxygenator or a blood reservoir.

According to a fourth aspect of the present invention, there is provideda medical instrument wherein at least the blood flow channel section iscoated in part or in its entirety by a polymer containing hydroxyethylmethacrylate (HEMA) and methyl methacrylate (MMA).

Preferably, hydroxyethyl methacrylate (HEMA) and methyl methacrylate(MMA) exist separately as respective separate segments. Preferably, theweight ratio of the segments containing hydroxyethyl methacrylate (HEMA)to the segments containing methyl methacrylate (MMA) is 50:50 to 95:5.More preferably, the content of hydroxyethyl methacrylate (HEMA) in saidsegment containing hydroxyethyl methacrylate (HEMA) is not less than 50wt. % and wherein the content of methyl methacrylate (MMA) in saidsegment containing methyl methacrylate (MMA) is not less than 70 wt. %.

Additionally, after the medical instrument is treated by the polymercontaining HEMA and MMA, it is treated by apoly(oxyethylene)-poly(oxypropylene) block polymer having the generalformula ##STR1## Preferably, a+c and b in the above formula are 2 to2000 and 10 to 150, respectively.

Preferably, the medical instrument is an oxygenator and the blood flowchannel section is the outer wall of porous hollow fibre housed withinthe oxygenator or a blood reservoir.

The medical instruments also include a blood reservoir and a bloodfilter.

The medical instruments further include components of a pump oxygenatorsuch as the aforementioned pump oxygenator, blood reservoir or bloodfilter and a pump oxygenating circuit system formed by these components.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a longitudinal cross-sectional view showing an embodiment of ablood reservoir according to the present invention and a prior artdevice.

FIG. 2 is a front view, partially broken away and showing a pumpoxygenator having hollow fibres according to the present invention.

FIG. 3 is a cross-sectional view of a blood filter.

FIGS. 4 and 5 are diagrammatic views showing a pump oxygenating circuitsystem.

DETAILED DESCRIPTION OF THE INVENTION

A hollow fibre type oxygenator according to a first aspect and a bloodreservoir according to a second aspect of the present invention will bedescribed in detail with reference to a blood reservoir of the type tobe built into the oxygenator according to a preferred embodiment of thepresent invention.

The hard shell type blood reservoir 1 incorporated to the oxygenator isshown diagrammatically in FIG. 1 and formed by a housing 7 formed of ahard material and including a blood inlet port 2, a blood influentsection 5 communicating with the inlet port and presenting a bottomsurface having substantially no drop from the inlet port 2, a bloodreservoir or storage section 6 communicating with the blood influentsection and presenting a bottom surface gradually descending from thesection 5 and a blood outlet port 3 formed at the bottom of thereservoir section 6. It is noted that the bottom surfaces of the bloodinfluent section 5 and the blood reservoir section 6 and the lateralsides of the housing 7 represent a blood flow channel surface 4.

The above described blood reservoir is provided within an excorporealcirculating circuit of the oxygenator. It is however more preferred thatthe blood reservoir be used as an oxygenating unit in which it iscombined as one with the oxygenator and a heat exchanger, as shown forexample in FIG. 2.

In the preferred embodiment shown in FIG. 2, an oxygenator 11 includes ahousing formed by a main body of the housing 12 and attachment covers13a, 13b closing both open ends of the main body of the housing 12.There are provided within the housing a multiplicity of hollow fibres 14parallel to and spaced apart from one another along the longitudinaldirection of the housing.

These hollow fibres 14 are maintained liquid-tightly with respect to themain body of the housing 12 by partition walls 15a, 15b at the both endswith the ends of the fibres remaining open.

A gas inlet space 16 formed by the attachment cover 13a, main body ofthe housing 12 and the partition wall 15 so as to be in communicationwith the inner space of the hollow fibres communicates in turn with agas inlet port 17, and a gas discharge space 18 formed by the attachmentcover 13b, main body of the housing 12 and the partition wall 15b so asto be in communication with the inner space of the hollow fibrescommunicates in turn with a gas discharge port 19b.

A blood chamber 20 defined by the inner wall of the main body of thehousing 12, partition walls 15a, 15b and the outer walls of the hollowfibres 14 communicates with a blood inlet port 21 and a blood outletport 22.

The oxygenator 11 shown herein is of the type in which gas exchange isperformed with the oxygen-containing gas such as air being blown in theinner space of the hollow fibres 14 and with the blood being caused toflow on the outer sides of the hollow fibres 14.

The hollow fibres 14 may be formed of any suitable hydrophobic materialscustomarily used for oxygenators. For example, polytetrafluoroethylene,polypropylene or silicone is preferred.

To the blood outlet 22 of the oxygenator 11, there is connectedliquid-tightly the blood inlet port 2 of the blood reservoir 1 describedwith reference to FIG. 1.

A heat exchanger 23 is connected to the blood outlet 21 of theoxygenator 11. The heat exchanger 23 includes a casing 24 in which amultiplicity of heat exchanger tubes 25 are arranged parallel to and ata spacing from one another along the length of the casing 24. The bothends of the heat exchanger tubes 25 are held liquid-tightly with respectto the side walls of the casing 24 by partition walls, not shown, withthe opening ends of the tubes remaining open.

A spacing 26 defined by these partition walls, side walls of the casing24 and the outer walls of the heat exchanger tubes 25 is kept incommunication with a blood inlet port 27 and the blood inlet 21 to theoxygenator 11. The inner spacing of the heat exchanger tubes 25liquid-tightly separated from the spacing 26 is kept in communicationwith a water inlet port 28 communicating with the outer side of one ofthe partition walls of the casing 24 and a water outlet port, not shown,communicating with the outer side of the other partition wall of thecasing 24.

In the above described heat exchanger 23, the blood flows into the heatexchanger 23 via blood inlet port 27 to flow along the outer sides ofthe heat exchanger tubes 25, while warm or cold water flows in theinside of the heat exchanger tubes 25 to warm or chill the bloodcontacting with the heat exchanger tubes 15. However, it is alsopossible to use a heat exchanger of the type in which the blood flows inthe inside of the heat exchanger tubes and the cooling or heating mediumis caused to flow in the outer sides of the heat exchanger tubes.

It is an important feature of the present invention that part or all ofthe blood flow channel surface from the blood inlet 21 to the bloodoutlet 22 in the above exemplified oxygenator on which the blood islikely to contact with oxygenator components, especially the hollowfibres, is subjected to a hydrophilizing treatment. It is not alwaysnecessary that the totality of the hollow fibres making up the hollowfibre bundle be hydrophilized. For example, more than half the hollowfibres may be hydrophilized and arrayed uniformly alternately with theremaining unhydrophilized fibres. In the event that the central portionof the hollow fibre bundle is constricted and throttled axially by thehousing of the oxygenator, it suffices that at least this constrictedportion be hydrophilized.

According to the present invention, as already described with referenceto the blood reservoir exemplified in FIG. 1, all or part of the bloodflow channel surface of the blood reservoir exhibits hydrophilicproperties. It may be the material constituting the blood flow channelsurface itself that exhibits these properties.

There are a number of methods of hydrophilizing the blood flow channelsurface. The following summarizes some of these methods that may beemployed in connection with the present invention.

(1) Acid Treatment

The acids that may be employed include KM_(n) O₄ /H₂ SO₄ and K₂ Cr₂ O₄H₂ SO₄ solutions. Above all, the KM_(n) O₄ /H₂ SO₄ solution ispreferred. For hydrophilizing treatment, the concentrations of 0.05 to 1wt. % and KM_(n) O₄ and 90 to 100 wt. % of H₂ SO₄ are preferred as theconcentrations of the components of the above solution.

In addition to the above acid mixtures, acids such as H₂ SO₄ may be usedalong.

(2) Treatment with an Albumin Aqueous Solution

An Albumin aqueous solution of 0.5 to 8 w/v % may be convenientlyemployed for hydrophilizing treatment.

(3) Treatment with PHEMA

This is the treatment with PHEMA or polyhydroxyethyl methacrylate. Forthe intended hydrophilizing treatment, the concentration of 0.05 to 4wt. % is preferred.

(4) Corona Discharge Treatment

In the corona discharge treatment, the corona discharge is caused tooccur on a material to introduce hydrophilic groups on the materialsurface. The duration of processing is set in dependence upon the degreeof the required hydrophilization.

(5) Plasma Treatment

In plasma processing, active species produced by the glow discharge areused to treat the polymer surface. The duration of processing is againset in dependence upon the degree of hydrophilization required.

(6) Ozone Treatment

In the ozone treatment, ozone is caused to occur on a material tointroduce hydrophilic groups on the material surface. The duration ofprocessing is set in dependence upon the degree of hydrophilizationrequired.

As described above, various methods may be employed for hydrophilizingthe oxygenator. For easiness of understanding, the degree ofhydrophilization may be evaluated in terms of wettability by water.

A hollow fibre may be said to be endowed with hydrophilic propertieswhen the water surface rises along the outer wall of the fibreintroduced into water from the direction normal to the water surface.

When the fibre is not hydrophilized, that is, not subjected to ahydrophilizing treatment, the water surface becomes concave along theouter wall of the hollow fibre.

In a material by which the blood reservoir of the present invention isformed, a contact angle with water of not more than 90 degrees,preferably up to 80 degrees may endow satisfactory wettability with bothpriming solution and blood.

Operation

In the oxygenator unit shown in FIG. 2, in which the blood reservoir 1is integrated with the oxygenator 11 and the heat exchanger, the bloodflowing into heat exchanger 23 via blood inlet port 27 is heated orcooled until it arrives at the blood inlet port 21 of the oxygenator 11.The blood flowing into the oxygenator 11 via blood inlet 21 undergoesgas exchange with the oxygen-containing gas via hollow fibres 14 withthe oxygen-containing gas circulated through the inside of the hollowfibres 14, as the blood flows through the blood chamber 20, such thatcarbon dioxide in the blood is removed while the consumed oxygen isreplenished.

It is noted that, since the blood flow channel surface of oxygenatorcomponents, above all, preferably the overall surface of the outer walls14a of the blood flow channel surface of the hollow fibre 14, ishydrophilized by the above described hydrophilizing treatment, forimproving wettability by the blood, there is no risk that the fiberswill be flocculated by the air to form cavities, as in the abovedescribed prior art. On the other hand, the blood may flow smoothly intothe blood chamber 20 without stagnation so that the gas exchange maytake place efficiently.

The blood thus replenished with oxygen exits at the blood outlet 22 ofthe oxygenator 11 to flow into the blood reservoir 1 via blood inletport 2 of the blood reservoir 1. The blood thus introduced via bloodinlet port 2 then reaches the blood influent section 5 communicatingwith the port 2 to flow smoothly on the blood flow channel surface 4 toflow down quietly into the blood reservoir section 6 for storagetherein.

Heretofore, the housing 7 of the blood reservoir 1 was formed of ahydrophobic material, such as hard vinyl chloride resin, styrene resinor carbonate resin. For this reason, the blood flow channel surfacepresents hydrophobic properties. Thus, in the event of bloodlesspriming, the priming liquid does not flow on the overall surface of theblood flow channel surface 4, but flows unevenly, causing disturbancesin the liquid stream. Thus an inconvenience is caused that the primingliquid flows into the blood reservoir section 6 as a waterfall dropsinto a pond so that the priming liquid forms bubbles in the bloodreservoir section.

According to the present invention, the blood flow channel surface 4 ofthe blood reservoir 1 described with reference to FIG. 1 ishydrophilized by the above described methods of hydrophilizing treatmentwhereby the wettability of the channel surface by the blood and thepriming liquid is improved. The blood and the priming liquid do not flowunevenly or at one time on the blood flow channel surface 4, but forms auniform flow as a whole to prevent foaming.

The present invention will be explained further in connection with amedical instrument according to third and fourth embodiments of theinvention.

According to the present invention, the material coating at least theblood flow channel section of the medical instrument in part or as awhole by way of a hydrophilizing treatment is preferably hydroxyethylmethacrylate (abbreviated hereafter to HEMA) and methyl methacrylate(abbreviated hereafter to MMA). It is because these polymers have a highdegree of safety, adaptability to blood, bioadaptabilty and polymersynthesis and coating can be made easily.

It is preferred that the polymer containing HEMA and MMA be in the formof a block copolymer in which HEMA and MMA are bonded together asseparate segments. It is also preferred that the segments existseparately in the polymer, since then the segments containing MMAexhibiting high water-proofness can be intimately bonded to the basematerial while the segments containing HEMA exhibiting hydrophilicproperties can be disposed on the surface to provide for a surfacehydrophilizing treatment having high degree of stability.

It is also preferred that the weight ratio of the HEMA containingsegment, referred to hereafter as A segment, to the MMA containingsegment, referred to hereafter as B segment, be 50:50 to 95:5. By the Asegment and the B segment herein are meant those fragments or portionsmainly containing HEMA and MMA, respectively. With the weight ratio ofthe A segment to B segment is less than 50:50, the hydrophilicproperties on the surface are lowered. With a weight ratio in excess of95:5, the coating polymer is likely to be eluted or peeled during usage.

It is also preferred that the contents of HEMA in the A segment be notlower than 50 wt. % and that the content of MMA in the B segment be notlower than 70 wt. %. With a content of HEMA in the segment A less than50 wt. %, the hydrophilic properties are lowered. With a content of MMAin the polymer less than 70 wt. %, tightness of bonding of the segmentto the base material is lowered, depending on the properties of polymercomponents other than MMA.

It is noted that, according to the present invention, there is nospecific limitation to the method of coating the polymer containing HEMAand MMA on the medical instrument and practically any method of coatingmay be employed.

Although a number of methods may be contemplated for preparing thepolymer employed in the present invention, one may use a methodincluding producing an acrylic polymer having peroxy bonds in the mainchain (HEMA containing polymer) and effecting dispersion polymerization,using this polymer as the polymerization initiator, to produce a blockcopolymer with a MMA containing polymer.

According to a third aspect of the present invention, the medicalinstrument is preferably a porous hollow fibre housed within anoxygenator or a blood reservoir. In any case, at least the blood flowchannel section thereof is coated in part or as a whole by the abovedescribed polymer to improve wettability by blood and adaptability orcompatibility to blood

Thus, in the blood reservoir, the polymer is coated mainly on the bloodflow channel surface of the housing to render the flow of the primingliquid and the blood to the blood reservoir section more smooth. In theporous hollow fibre, one of the inner and outer walls of the hollowfibre is used in general as the blood flow channel surface. However, thepresent invention is applied to the hollow fibre, the outer wall ofwhich, above all, is used as the blood flow channel surface. Thus theouter wall of the hollow fibre is coated with the above polymer toimprove wettability by blood and to render the blood stream more smooth.

In this manner, adaptability to the blood of the hollow fibre may beimproved simultaneously.

It is to be noted that portions other than the portions forming theblood flow channel surface may also be subjected to the above describedhydrophilizing treatment.

According to a fourth aspect of the present invention, for improvingwettability, after the blood flow channel section of the medicalinstrument is processed and coated with the above polymer containingHEMA and MMA, it is processed and treated with apoly(oxyethylene)-poly(oxypropylene) block polymer represented by thefollowing general formula (I) ##STR2## It is noted that there is nospecific limitation to means of coating the medical instrument with theblock copolymer and any known methods for coating may be employed.

In this manner, wettability and the properties of preventing foamdeposition or affixture may be improved simultaneously. For obtainingthe above results for the medical instrument of the present inventiona+c in the above is 2 to 2000, preferably 2 to 500 and more preferably 3to 300, and b is 10 to 150, preferably 10 to 100 and more preferably 15to 70. Outside of these ranges, hydrophilic properties of the blockcopolymer itself are lowered or the affinity to the hydrophobic sectionis lowered, so that wettability on the surface of the material followingthe processing is correspondingly lowered.

The medical instruments according to a fourth aspect of the presentinvention include those instruments and components thereof likely tocome into contact with blood, such as in a circuit for cardiopulmonaryby-pass, artificial dialysis system, blood plasma separating system anda variety of catheters. In the case of the circuit for cardiopulmonaryby-pass, the medical instruments means both the respective componentsmaking up the system and the system in its entirety. The componentsmaking up the system include an oxygenator, above all, a film ormembrane type oxygenator, a blood reservoir, such as arterial reservoir,vena reservoir or cardiotomic reservoir, bubble trap, centrifugal pumpand tubes connecting these components. In any of the above case, atleast the blood flow channel sections of these components are coated inpart or as a whole by the above polymer to improve wettability by blood,adaptability or compatibility to blood and the properties of preventingaffixture of air bubbles.

That is to say, in the blood reservoir, the above polymer is coatedmainly on the blood flow channel surface of the housing to render theflow of the blood and the priming liquid to the blood reservoir sectionmore smooth. In the case of the porous hollow fibre within theoxygenator, one of the inner and outer walls of the hollow fibre is usedas the blood flow channel surface. Especially, in the case of the hollowfibre the outer wall side of which is used as the blood flow channelsurface, the outer wall of the hollow fibre can be coated with the abovepolymer to improve wettability by blood to render the blood flow moresmooth.

In this manner, the adaptability to blood of the hollow fibre is alsoimproved simultaneously. In the case of the hollow fibre the inner wallof which is used as the blood flow channel surface, the inner wall ofthe fibre may also be coated with the above polymer to improve theproperties of preventing formation of air bubbles and adaptability toblood.

It is to be noted that the portions of the hollow fibre other than thoseforming the blood flow channel surface may also be subjected to theabove described hydrophilizing treatment.

The medical instrument according to the present invention includes ablood flow filter 30 shown in cross-section in FIG. 3. This filter isincorporated into, for example, a pump oxygenating circuit to effectultimate defoaming at the time the blood is returned into the patient'sbody.

The blood flow filter 30 has a housing 31 having an upper air dischargeport 32, a central blood inlet port 33 and a lower blood outlet port 34.

A filter medium 35 formed by a polyester net is provided between theblood inlet port 33 and the blood outlet port 34.

The blood introduced into the blood inlet port 32 flows down the wall ofthe housing 31 as it gyrates to reach the filter medium 35. During thistime interval, the blood defoamed by the filter material 35 is returnedto the patient's body via outlet port 34, while the air removed from theblood is discharged via air outlet port 34.

Such blood filter is also preferably processed by a polymer containingHEMA and MMA or in addition thereto with the block copolymer representedby the above general formula (I), similarly to the blood reservoir orthe pump oxygenator described above. In this manner, the defoamingproperties are improved, while the priming time is reduced as a resultof improved wettability. In a hard shell type blood reservoir, one ormore components 36 in the form of a sponge and/or a net may be providedhalfway in the blood flow channel for improving the defoaming efficiencyand removal of impurities. In this case, only the aforementionedcomponents or the blood reservoir including these components in itsentirety may be processed by the above polymer to defoam the trapped airbubbles quickly.

FIG. 4 shows an example of a pump oxygenating circuit system 40including the aforementioned blood reservoir, pump oxygenator and bloodfilter. In this system, the blood reservoir 42, pump 43, oxygenator 45with a heat exchanger 44 and a blood filter 30 are interconnected with ahuman body 41 by a tube 46 to form an excorporeal circulating circuit.

Such circuit as a whole is preferably processed with the aforementionedpolymers containing HEMA and MMA or with the block polymer representedby the general formula (I) to provide for improved wettability and theproperties of preventing affixture of air bubbles.

OPERATION

The operation of an oxygenator including a blood reservoir and poroushollow fibres as the medical instrument of the present invention will beexplained in more detail.

It is a feature of the present invention that the blood flow channelsurface 4 of the blood reservoir 1 of FIG. 1 is coated in part or as awhole by the polymer containing HEMA and MMA or in addition thereto bythe block polymer represented by the above general formula (I) toprevent wettability by blood and the properties of preventing affixtureof air bubbles.

With the blood flow channel surface 4 being thus coated with the polymercontaining HEMA and MMA or further with the block copolymer representedby the above general formula (I) by way of a hydrophilizing treatment,the blood and the priming liquid introduced at the blood inlet port 2 iscaused to flow smoothly on the blood flow channel surface 4 withoutbecoming stagnant so that it flows smoothly on the gradually descendingsurface until it reaches the blood reservoir section 6. In this manner,the blood and the priming liquid are caused to flow quietly within theblood reservoir section 6 without any disturbances in the liquid flow orresultant foaming as in the prior art system.

The above described blood reservoir is provided within the excorporealcirculating blood circuit. However, it is preferably combined with anoxygenator and a heat exchanger to form an oxygenating device or system,as shown for example in FIG. 2.

In the embodiment shown in FIG. 2, the oxygenator 11 has a housingformed by a cylindrical main body of the housing 12 and attachmentcovers 13a, 13b closing both open ends of the main body of the housing12. Within the entire region of the housing, a bundle of a multiplicityof hollow fibres 14 is arranged along the length of the housing so thatthe fibres are juxtaposed to and spaced apart from one another.

The both ends of the hollow fibres 14 are supported liquid-tightlyagainst the main body of the housing 12 by partition walls 15a, 15b,with the ends of the fibres being not closed. A gas inflow space 16formed by the attachment cover 13a, main body of the housing 12 and thepartition wall 15 so as to be in communication with the inner space ofthe hollow fibres communicates in turn with a gas inflow port 17, and agas outflow space 18 formed by the attachment cover 13b, main body ofthe housing 12 and the partition wall 15b so as to be in communicationwith the inner space of the hollow fibres communicates in turn with agas outflow port 19b.

A blood chamber 20 defined by the inner wall of the main body of thehousing 12, partition walls 15a, 15b and the outer walls of the hollowfibres 14 communicates with a blood inlet port 21 and a blood outletport 22.

The oxygenator 11 shown herein is of the type in which gas exchange isperformed with the oxygen-containing gas such as air being blown in theinner space of the hollow fibres 14 and with the blood being caused toflow on the outer sides of the hollow fibres 14.

The hollow fibres 14 may be formed of any suitable hydrophobic materialscustomarily used for oxygenators. For example, polytetrafluoroethylene,polypropylene or silicon is preferred.

According to the present invention, the outer wall 14a forming the bloodflow channel surface of the hollow fibres 14 is preferably coated as awhole by the polymer containing HEMA and MMA or further with the blockcopolymer represented by the above general formula (I) and therebyhydrophilized to improve wettability thereof by blood.

The hollow fibre type oxygenators developed heretofore were generally ofthe type in which the blood is caused to flow within the interior of thehollow fibres. However, because of larger pressure losses encountered,the hollow fibre type oxygenators can be adapted only difficultly topulsapile perfusion, separate excorporeal circulation or to bloodcardioplegia.

The hollow fibre formed by a hydrophobic resin exhibits poor surfacewettability by blood so that the blood is not permeated in to the spacebetween the adjacent hollow fibres and an efficient gas exchange via thehollow fibres is obstructed with the result that sufficient gas exchangeproperties are not obtained. For wetting the outer wall surface of thehollow fibres, air bubbles remaining within the space between the hollowfibres need be removed by a laborious operation of imparting a physicalshock to the oxygenator, such as by striking.

Thus, with the blood being caused to flow outside of the hollow fibresand the gas within the inner space of the fibres, pressure losses may bereduced, such that the blood can be supplied to the oxygenator andthence to the blood reservoir by the blood being taken out by thepressure head from the patient's body without the necessity of providinga blood delivery pump ahead of the oxygenator in the circulatingcircuit. Thus the oxyenator can be adapted to blood cardioplegia orseparate excorporeal circulation.

To the blood outlet 22 of the oxygenator 11 is liquid-tightly connectedthe blood inlet port 2 of the blood reservoir 1 described with referenceto FIG. 1.

A heat exchanger 23 is connected to the blood outlet of the oxygenator11. The heat exchanger 23 includes a casing 24 in which a multiplicityof heat exchanger tubes 25 are arranged parallel to and at a spacingfrom one another along the length of the casing 24. The both ends of theheat exchanger tubes 25 are held liquid-tightly with respect to the sidewalls of the casing 24 by partition walls, now shown, with the openingends of the tubes remaining open.

A spacing 26 defined by these partition walls, side walls of the casing24 and the outer walls of the heat exchanger tubes 25 is kept incommunication with a water inlet port 28 communicating with one of thepartition walls of the casing 24 and a water outlet port, not shown,communicating with the outer sides of the other partition wall of thecasing 24.

In the above described heat exchanger 23, the blood flows into the heatexchanger 23 via blood inlet port 27 to flow along the outer sides ofthe heat exchanger tubes 25, while warm or cold water flows in theinside of the heat exchanger tubes 25 from the water inlet port 28 towarm or chill the blood contacting with the heat exchanger tubes 15.However, it is also possible to use a heat exchanger of the type inwhich the blood flows in the inside of the heat exchanger tubes and thecooling or heating medium is caused to flow on the outer sides of theheat exchanger tubes.

In the oxygenating unit in which the blood reservoir 1 is integrated tothe oxygenator 11 and the heat exchanger 23, the blood flowing into theinside of the heat exchanger 23 via the blood inlet port 27 is heated orchilled until it reaches the blood inlet 21 of the oxygenator 11. Theblood flowing from the blood inlet 21 of the oxygenator 11 undergoes agas exchange with the oxygen containing gas flowing in the inside spaceof the hollow fibre 14, as the blood flows through the blood chamber 20,so that excess carbon dioxide in the blood is removed, while oxygen isreplenished to supplement consumed oxygen.

Preferably the overall surface of the outer wall 14a of the hollowfibres 14 acting as the blood flow channel surface is covered by theHEMA ot MMA containing polymer or further thereon the block polymerrepresented by the above general formula (I) and thereby hydrophilizedto improve the wettability by the blood and the properties of preventingaffixture of air bubbles, so that there is no rick for the fibers to beflocculated by the air to form so-called cavities as in the abovedescribed prior art system. In addition, the blood may flow smoothlyinto the blood chamber 20 without residing there so that the gasexchange may be performed efficiently.

The blood thus replenished with oxygen flows out at a blood outlet 22 ofthe oxygenator 11 to flow then into the blood reservoir 1 via the bloodinlet 2 of the blood reservoir 1 communicating with the outlet 22. Theblood introduced via the blood inlet 2 then reaches the blood influentsection 25 contiguous to the blood inlet 2 to pass by the defoamingmember 36 to flow smoothly on the blood flow channel surface 4 coated bythe polymer containing HEMA and MMA or in addition thereto the blockpolymer of the formula (I) to flow down quietly and stored in the bloodreservoir section 6 without forming air bubbles in the blood reservoirsection 6. These effects in the blood reservoir 1 are most outstandingat the time of bloodless priming.

The blood thus stored in the blood reservoir section 6 without formingair bubbles is let out at the blood outlet 3 at the lower portion of theblood reservoir section 6 for blood delivery.

And due to improvement of adaptability to blood, it is expected thatdecrease of platelets is restrained.

It is noted that the description of the above embodiment has been madewith reference to hollow fibres in an oxygenator. However, the presentinvention is not limited thereto but may also be applied to hollowfibres employed for example in hemoconcentrators.

In the blood filter shown in FIG. 3, the properties of preventingaffixture of air bubbles and adaptability to blood are improved, as inthe preceding embodiment. In addition, when the blood filter isprocessed with the block copolymer represented by the general formula(I), among the aforementioned polymers, wettability of the net-likefilter material is improved to facilitate the priming operation.

The same applies for the pump oxygenating circuit system shown in FIGS.4 and 5.

EXAMPLES

The description with reference to certain Examples will be givenhereinbelow for illustration of the present invention.

Examples for First Aspect of the Invention Comparative Example

Using 34000 microporous polypropylene hollow fibres, each 300 microns inoutside diameter, an oxygenator having a film or membrane area of 3.1 m2was prepared.

Exampe 1

A 0.4% solution of KM_(n) O₄ /conc. H₂ SO₄ was charged into anoxygenator prepared similarly to the Comparative Example. While thenarrow portion of the oxygenator was struck, the oxygenator was allowedto stand for five minutes, and the liquid inside the oxygenator wasdischarged. The oxygenator was washed with water and dried in air.

Example 2

2 liters of a 4% albumin solution was circulated in the oxygenatorprepared similarly to Comparative Example at the rate of 2 liters perminute as the constricted portion of the oxygenator was stuck. Theoxygenator was then dried in air.

Example 3

A methanol solution containing 1 w/v % of PHEMA was charged into anoxygenator prepared in the same manner as in Comparative Example. Whilethe constricted portion of the oxygenator was stuck, the oxygenator wasallowed to stand for one minute. After the liquid inside the oxygenatorwas discharged, the oxygenator was dried in air.

Example 4

Using a corona discharge units HFS 202 produced by Kasuga Denki KK, thesame hollow fibres of microporous polypropylene as those employed inComparative Example, were taken up on a bobbin at a take-up speed of 50mm/min, while the current of 6.5 A at 120 V was caused to flow in anelectrode 10 mm wide and 20 mm long, wound by a Teflon sheet 80 micronsthick. Then, using these hollow fibres, and oxygenator similar to thatused int he Comparative Example was assembled.

Example 5

The hollow fibres same as those used in the Comparative Example were cutto lengths of 50 cm and arrayed within a tank so as to avoid stacking.The fibres were then subjected to plasma processing at 100 W for twominutes at 10⁻¹ torr and 30° to 40° C. Using the thus produced plasmaprocessed hollow fibres, an oxygenator similar to that used inComparative Example was prepared.

Example 6

After a gas port of an oxygenator prepared in the similar manner as inComparative Example, ozone was introduced for ten minutes via a bloodinlet port. Then, after ozone was similarly introduced via blood outletport for ten minutes, the outer wall of the hollow fibre was subjectedto a hydrophilizing treatment.

Test Example 1

The ability of oxygen addition of the oxygenators prepared inComparative Example and Examples 1 to 6 was measured in accordance withAAMI standards. The results are shown in Table 1. With regard to theproperties of the oxygenators shown in Table 1, the indications givenbelow have the following meanings:

Before striking: The oxygen addition ability of the blood was measuredimmediately after priming of the oxygenator with the cow's blood.

After striking: The oxygen addition ability of the blood was measuredafter the constricted mid portion of the oxygenator was stuck stronglywith forceps as the blood was circulated after termination of the abovepriming.

                  TABLE 1                                                         ______________________________________                                                   Ability of Oxygen Addition                                                    Before Striking (%)                                                                       After Striking (%)                                     ______________________________________                                        Comparative Example                                                                        13            100                                                Example 1    96            100                                                Example 2    100           100                                                Example 3    95            100                                                Example 4    90            100                                                Example 5    93            100                                                Example 6    96            100                                                ______________________________________                                    

Test Example 2

Tests were conducted for measuring hydrophilic properties of the hollowfibres employed in oxygenators produced in Comparative Example andExamples 1 to 6. beaker was filled with water and each one of the abovehollow fibres was inserted into water from above orthogonally to thewater surface. As a result, a meniscus was formed at the boundarybetween the outer wall of the hollow fibre and the liquid surface. Inthe case of fibres of the Comparative Example, the liquid surface wasseen to be concave toward below along the outer wall of the hollowfibre, whereas, in the fibres of the Examples 1 to 6, the liquid surfacewas seen to rise along the outer wall of the fibre, thus indicating thathydrophilic properties were endowed to these fibres.

Examples For Second Aspect of the Invention Comparative Example

A blood reservoir as shown in FIG. 1 was prepared by injection moldingof a polycarbonate resin.

Example 1

After the blood flow channel surface of a blood reservoir preparedsimilarly to the Comparative Example was dipped for five minutes in a0.4% KM_(n) O₄ /conc. H₂ SO₄, the liquid inside the reservoir wasdischarged and the reservoir was then washed with water and dried inair.

Example 2

A blood reservoir prepared in the similar manner to Comparative Examplewas filled with a 4% albumin solution and allowed to stand stationaryfor one minute. The liquid inside the blood reservoir was discharged andthe blood reservoir was dried in air in a clean bench.

Example 3

A blood reservoir prepared in the similar manner to Comparative Examplewas filled with a methanol solution containing 0.2 w/v % of PHEMA andallowed to stand stationary. The liquid inside the blood reservoir wasdischarged and the blood reservoir was dried in air in a clean bench.

Example 4

Using a corona discharge unit HFS 202, produced by Kasuga Denki KK, theblood flow channel surface of a blood reservoir prepared in ComparativeExample was subjected to a corona discharge treatment with the currentof 5 A at 120 V being caused to flow in an electrode which is 10 mm wideand 20 mm long and which is wound by a Teflon sheet 80 microns thick.

Example 5

A blood reservoir produced in Comparative Example was subjected toplasma processing in a tank at 100 W for two minutes at a pressure of10⁻¹ torr and at a temperature of 30° to 40° C.

Example 6

A blood reservoir produced in Comparative Example was placed in a glassdesiccator. After the temperature within the desiccator was set to 50°C., O₂ was caused to flow into an ozone generator at a flow rate of 0.8liter per minute to produce ozone at 100 V, with the so-produced ozonebeing caused to flow into the desiccator. After this processing wascarried out for 20 minutes, the inside space of the desiccator wasreplaced by O₂. The blood reservoir was then taken out of the desiccatorto terminate the ozone processing.

Test Example 1

The blood flow channel surfaces of the blood reservoirs produced inaccordance with the Comparative Example and Examples 1 to 6 werepartially cut off to measure the contact angle with respect to water.The results are as shown in Table 2.

                  TABLE 2                                                         ______________________________________                                                      Contact Angle (degrees)                                         ______________________________________                                        Comparative Example                                                                           92                                                            Example 1       40                                                            Example 2       33                                                            Example 3       39                                                            Example 4       49                                                            Example 5       65                                                            Example 6       62                                                            ______________________________________                                    

Test Example 2

With 300 ml of physiological saline water being stored in bloodreservoir sections of the blood reservoir produced in ComparativeExample and Examples 1 to 6, physiological saline water was caused toflow on the blood flow channel section at a flow rate of 4 liters perminute and the manner in which the physiological saline water flows onthe blood channel surface and the generation of air bubbles in the bloodreservoir sections were observed. The results are shown in Table 3.

                  TABLE 3                                                         ______________________________________                                                              Foaming State at                                               Blood Flow State                                                                             Blood Storage Section                                   ______________________________________                                        Comparative                                                                            Two to three steak-like                                                                        marked foaming                                      Example  blood flows were observed                                            Example 1                                                                              Blood flowed on the                                                                            no foaming                                                   overall flow channel since                                                    it started to flow                                                   Example 2                                                                              same as above    same as above                                       Example 3                                                                              same as above    same as above                                       Example 4                                                                              same as above    same as above                                       Example 5                                                                              same as above    same as above                                       Example 6                                                                              same as above    same as above                                       ______________________________________                                    

EMBODIMENTS FOR THIRD AND FOURTH ASPECTS OF THE INVENTION Example 1 andComparative Examples 1 and 2

By way of Example 1, a 2% (methanol/methyl cellosolve=92/8) blockcopolymer of MMA (B segment)/HEMA (A segment) was coated in the state ofa solution of a microporous polypropylene flat film. Also, by way ofComparative Example 1, the above microporous polypropylene flat film wasnot subjected to any treatment such as hydrophilizing treatment.Finally, by way of Comparative Example 2, a 2% PHEMA solution inmethanol was coated on a flat microporous polypropylene film tohydrophilize its surface. Using these films, the following tests on theproperties were conducted.

i) Contact Angle

The contact angle of the surface of the polymer of Example 1 withrespect to water was measured and found to be equal to 62°. After thepolymer of Example 1 was allowed to stand in the polymer-coated state atroom temperature for five days, the contact angle was again measured,and found to be substantially not changed.

The contact angle of the flat film of Comparative Example 1 with respectto water was about 109°, while that of the flat film of ComparativeExample 2 was 64°. It has thus been shown that the above coating by thepolymer results in the hydrophilized film.

ii) Tests on Ability to Expand Platelet

By way of tests on platelet spread ability test, the human blood wastreated by a 1/10 vol. part of a 3.8% sodium citrate solution againstcoagulation and centrifuged for 15 minutes at 800 r.p.m. The supernatantwas sampled and adjusted to a concentration of 60,000 per microliter bya diluent (physiological saline water/3.8% sodium citrate=9/1). Thesupernatant thus treated was dropped on film samples and allowed tostand for 30 minutes, after which the form and the number of the affixedplatelets were checked.

In Example 1, the rates of affixture was 85%, 15% and 0% for types I, IIand III, respectively, with the sum of the affixed platelets being467/0.5 mm2. In Comparative Example 1, the rates ere 49%, 23% and 28%for the types I, II and II, respectively, with the sum of the affixedplatelets being 1386/0.6 mm2 and, in Comparative Example 2, the samerates were 30%, 25% and 45% for types I, II and III, respectively, withthe sum of the affixed platelets being 1771/0.5 mm2.

It may be seen from this that coating the polymer of the Example in theabove manner results not only in improved hydrophilic properties, but inimproved blood adaptability.

The above classification into the types I, II and II has been made inaccordance with the classification found in "Reaction of Platelets onthe Surface of High Polymer Material for Medical Use" in "The JapaneseJournal of Artificial Organs" 9(1), 228 to 231 (1980).

iii) Tests on Eluates

Tests on eluates were conducted in accordance with the disposable setstandard for cardiopulmonary by-pass by the Ministry of Health andWelfare. Thus the circuit through which flowed the blood in thecardiopulmonary by-pass was filled with water which had been boiled andallowed to cool. Then, using a suitable tool, the ends of degasifyingtubes, oxygen blowing tubes and connecting tubes were closed. Thecircuit was then heated at 70°±1° C. for 30 minutes and cooled and theliquid contents were taken out as the test liquid and subjected to teststo be described later. The present oxygenator passed these tests.

The amount of consumption of potassium permanganate was withinprescribed limits in Example 1, but exceeded the limits in ComparativeExample 2.

Example 2 and Comparative Example 3

By way of Example 2, a polycarbonate food reservoir as shown in FIG. 1was prepared by injection molding and the blood flow channel surfacethereof was coated with the block polymer of Example 1 by the samemethod as that of Example 1. The contact angle of the blood flow channelsurface with respect to water was measured and found to be 38°.

On the other hand, a blood reservoir not coated with the polymer ofExample 2 was similarly prepared by way of Comparative Example 3. Thecontact angle of the blood flow channel surface with respect to waterwas measured and found to be 91°.

The blood storage sections of the blood reservoirs of the Example 2 andthe Comparative Example 3 were charged with 300 ml of physiologicalsaline water and physiological saline water was caused to flow on theblood flow channel surfaces of the blood reservoirs to check for themanner in which the physiological saline water flowed on the blood flowchannel surfaces and the manner in which the foam was generated in theblood storage sections.

It was now found that, in the Example 2, the physiological saline waterflowed uniformly and quietly on the blood flow channel surfaces in theirentirety and no foam was seen to be generated in the blood storagesections. However, in Comparative Example 3, two main thick flows wereseen approximately at the center of the blood flow channel surface withthree fine meandering flows about the central flows, and air bubbles orfoams were seen to be floating to and fro in the blood storage section.

Example 3 and Comparative Example 4

By way of Example 3, and oxygenator was prepared with the use of 34000microporous polypropylene hollow fibres of 300 μm in outside diameter,and a 2% (methanol/methylcellosolve=92/8) block copolymer solution ofMMA (B segment)/HEMA (A segment) was charged in the oxygenator, whichwas allowed to stand for one minute while the constricted portion of theoxygenator was struck, the liquid contents in the oxygenator being thendischarged and dried in air.

On the other hand, by way of Comparative Example 4, the same oxygenatorwas charged with a methanol solution containing 2 w/v % of PHEMA andallowed to stand for one minute while the constricted portion of theoxygenator was stuck, the liquid contents in the oxygenator being thendischarged and dried in air.

The oxygenators of Example 3 and Comparative Example 4 were thensubjected to tests on eluates in accordance with the disposable setstandard for cardiopulmonary by-pass by the Ministry of Health andWelfare. Thus the circuit through which flowed the blood of thecardiopulmonary by-pass was filled with water which had been boiled andallowed to cool. Then, using a suitable tool, the ends of degasifyingtubes, oxygen blowing tubes and connecting tubes were closed. Thecircuit was then heated at 70°±1° C. for 30 minutes and cooled and theliquid contents were taken out as the test liquid and subjected to thefollowing tests which the oxygenators under test must pass.

These tests include those on i) outward appearance and pH; ii) foaming;iii) degree of cleanliness; iv) lead and cadmium; v) zinc; vi) apotassium permanganate reducing substance; and vii) evaporationresidues.

In Example 3, the tested oxygenators were found to be within thereference standards for all of the tests. However, in ComparativeExample 4, in the test for the potassium permanganate reducingsubstance, the consumption of potassium permanganate exceeded thereference standards.

Example 4

Using the blood filter shown in FIG. 3, the following tests wereconducted. The housing of the blood filter was formed of polycarbonate,the filter medium was a polypropylene net having a mesh size of 380 meshand the blood filtration area was 750 cm².

The blood filter was charged with a 1% methanol solution of MMA (Bsegment)/HEMA (A segment)-20/80 and dried in air immediately after theliquid contents were discharged.

The blood filter was then charged with an aqueous solution of a blockpolymer having the above formula (I) wherein (a+c)=75 and b=30 (PluronicF-68 manufactured by BASF) and dried in air immediately after the liquidcontents were discharged.

A priming liquid (physiological saline solution) was charged into theinside of the filter medium in the so-produced blood filter from theblood outlet. At this time, the priming liquid was accumulated in theinside of the filter medium until the filter medium was wetted. When thefilter medium was wetted in this manner, the priming liquid stored inthe inside of the filter medium was spurted out via the filter mediumvigorously. The time elapsed since the charging of the priming liquiduntil ejection of the priming liquid out of the filter medium wasmeasured. With the filter medium exhibiting poor wettability, thepriming liquid was not discharged until a certain pressure drop wasestablished with the progress of charging of the priming liquid.

The measured results are shown in the following Table 4.

                  TABLE 4                                                         ______________________________________                                                       Efflux Time Duration (seconds)                                 Processing Method                                                                         remarks    1        10  20                                        ______________________________________                                        none        CX-AF      *************************                              polymer containing                                                                        1.0%       *************                                          HEMA and MMA                                                                  poly(oxyethylene)-                                                                        0.005%     ******                                                 poly(oxypropylene)                                                            block polymer                                                                 polymer containing                                                                        0.005%     ****                                                   HEMA and MMA                                                                  (1%)                                                                          +poly(oxyethylene)-                                                           poly(oxypropylene)                                                            block polymer                                                                 ______________________________________                                    

EFFECTS OF THE INVENTION

The oxygenator exhibits superior wettability by blood since the hollowfibres are hydrophilized by, for example, acid-, albumin-, PHEMA-,corona discharge- plasma- or ozone processing.

The result is that, since the air bubbles can be affixed onlydifficultly to the outer wall surfaces of the hollow fibres, the spacesbetween the fibers are not blocked by air bubbles and the blood may flowsmoothly so that the gas exchange may be performed efficiently.

The blood reservoir of the present invention exhibits superiorwettability by the priming liquid and the blood since the blood flowchannel surface, above all, exhibits hydrophilic properties.

The result is that the blood flows down uniformly down the blood flowchannel surface without flowing partially, so that it becomes possibleto prevent air bubbles from being formed when the blood flows from theblood flow channel surface into the blood storage section.

The present invention provides a safe medical instrument which ishydrophilizingly treated by that at least the blood flow channel sectionof the instrument is coated by a polymer containing HEMA and MMA or inaddition thereto a block polymer represented by the general formula (I)and thereby hydrophilized, and which also is superior in adaptability,to blood, so that the present invention may be applied extensively tohollow fibres or to blood reservoirs.

What is claimed is:
 1. A blood reservoir comprising:a blood inlet port,a blood influent section in liquid communication with the inlet port, ablood storage section in liquid communication with the blood influentsection, said blood storage section having at least a portion of theinner surface coated by a polymer containing hydroxyethyl methacrylate(HEMA) units and methyl methacrylate (MMA) units and being additionallycoated with a poly(oxyethylene)-poly(oxypropylene) block polymerrepresented by the general formula: ##STR3## wherein 2≦a+c≦2000 and10≦b≦150, and a blood outlet port.
 2. A blood reservoir comprising:ablood inlet port, a blood influent section in liquid communication withthe inlet port, a blood storage section in liquid communication with theblood influent section, said blood storage section having a bottomsurface gradually descending from the blood influent section whereinsaid bottom surface has a coating of a polymer containing hydroxyethylmethacrylate (HEMA) units and methyl methacrylate (MMA) units and isadditionally coated with a poly(oxyethylene)-poly(oxypropylene) blockpolymer represented by the general formula: ##STR4## wherein 2≦a+c≦2000and 10≦b≦150, and a blood outlet port formed at the bottom of the bloodstorage section, wherein said bottom surface is hydrophilic.
 3. Theblood reservoir according to claim 2, wherein the hydrophilic bottomsurface exhibits a contact angle with respect to water which is lessthan 90°.
 4. The blood reservoir according to claim 3, wherein saidcontact angle is not more than 80°.
 5. The blood reservoir according toclaim 2, wherein the polymer is a block copolymer and the HEMA units andthe MMA units are separate segments in the block copolymer.
 6. The bloodreservoir according to claim 5, wherein the weight ratio of the segmentscontaining the HEMA units to the segments containing the MMA units isfrom 50:50 to 95:5.
 7. The blood reservoir according to claim 5, whereinthe content of the HEMA units in said segments containing the HEMA unitsis not less than 50 wt % and the content of the MMA units in saidsegments containing the MMA is not less than 70 wt %.
 8. The bloodreservoir according to claim 2 wherein a, b and c in the general formulasatisfy the following conditions:2≦a+c≦500 and 10≦b≦100.